Blonanserin, AD-5423, Lonasen
Blonanserin
CAS: 132810-10-7
Molecular Formula: C23H30FN3
Blonanserin, AD-5423, Lonasen - Names and Identifiers
Blonanserin, AD-5423, Lonasen - Physico-chemical Properties
| Molecular Formula | C23H30FN3 |
| Molar Mass | 367.5 |
| Density | 1.095±0.06 g/cm3(Predicted) |
| Melting Point | 117-119°C |
| Boling Point | 540.8±50.0 °C(Predicted) |
| Flash Point | 280.9°C |
| Solubility | DMSO <1 mg/mL Water <1 mg/mL Ethanol <1 mg/mL |
| Vapor Presure | 9.21E-12mmHg at 25°C |
| Appearance | White to white-like powder |
| Color | white to off-white |
| Merck | 14,1319 |
| pKa | 7.66±0.10(Predicted) |
| Storage Condition | Sealed in dry,Room Temperature |
| Refractive Index | 1.557 |
| MDL | MFCD00893838 |
| Use | Drugs for the treatment of schizophrenia |
Blonanserin, AD-5423, Lonasen - Risk and Safety
| Hazard Symbols | Xn - Harmful |
| Risk Codes | 22 - Harmful if swallowed |
| WGK Germany | 1 |
| RTECS | GY0175140 |
| HS Code | 29339900 |
Blonanserin, AD-5423, Lonasen - Introduction
Blonanserin, a novel atypical antipsychotic, is a potent dopamine D2(Ki is 14.8 nM) and serotonin 5-HT2(Ki is 3.98 nM) receptor antagonist
Last Update：2022-10-16 17:13:25
Blonanserin, AD-5423, Lonasen - Reference Information
| Overview | This product is a serotonin and dopamine antagonist (SDA), is the second generation of atypical anti-schizophrenia drugs, it has the same dopamine D2 receptor blocking effect as haloperidol, and also has a strong blocking effect on 5-HT2A, and the selectivity of the two receptors is stronger than that of other antipsychotic drugs. The extrapyramidal side effect response is less than that of existing antipsychotics on the market. It was developed and listed by sumitomitsu Pharmaceutical Co., Ltd., Japan. Date of launch: it was launched in Japan in April 2008. |
| Basic information | bonanserin is a new drug for the treatment of schizophrenia, the chemical name is 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocyclooctane pyridine. It is a highly selective 5-HT2 (5-hydroxytryptamine II) receptor and D2 (dopamine II) receptor antagonist with less affinity for D1 and adrenergic α1, H1 histamine receptor and M1 choline receptor, it has the characteristics of high safety and less adverse reactions, and is mainly used in the treatment of atypical psychosis. |
| pharmacological action | 1. Receptor binding bunanserin has strong affinity for dopamine D2, D3 receptors and 5-HT2A receptors, its affinity for dopamine D2 receptors (inhibition constant Ki = 0.14nmol/L-1) is 20 times that of haloperidol (Ki = 2.73nmol/L-1), is 94-fold higher than that of risperidone (Ki = 13.2nmol/L-1); Compared with most other atypical antipsychotics, including risperidone, bonanserin has several times higher affinity for the dopamine D2 receptor than for the 5-HT2A receptor [2,3]. In vitro experiments, bunanserin on other neurotransmitter receptors such as dopamine D1, D2, D4, D5 receptor, 5-HT1A, 5-HT2B, 5-HT2C, 5-HT3~7 receptor, histamine H1 receptor, m1 choline receptors and Alpha 1, Alpha 2 and beta adrenergic receptors have low or very low affinity (Ki 26~14300mmol? L-1). The degree of antagonism of α1-adrenoceptor is believed to be related to the occurrence of such adverse reactions caused by antipsychotic drugs. The affinity of bunanserin for Alpha 1-adrenoceptors in the in vitro experiments was 1/3 of haloperidol and 1/40 of risperidone, these findings may explain, in part, why patients with schizophrenia have lower rates of orthostatic hypotension than those taking linoperazone. The N-deethylated metabolites of the bunanserin bunanserin have a higher affinity for dopamine D2, D3 receptors and 5-HT2A receptors, however, the affinity for most other receptors (including dopamine D1 receptor, α1-adrenoceptor, histamine H1 receptor and M1 choline receptor) is low. The affinity of N-desethylated bunanserin for 5-HT2C and 5-HT6 receptors is more than 3 times that of its prodrug. Notably, the pharmacological effect of N-desethylated bunanserin is a fraction of its prodrug in an in vitro animal model. 2. Central nervous system effects bonanserin generally attenuates dopamine-induced inhibition of neuronal firing in the medial prefrontal cortex of rats. Some animal models have shown that bunanserin has the possibility of causing extrapyramidal adverse reactions (EPS), and EPS is indeed the most common adverse reaction of bunanserin in the clinical treatment of schizophrenia. Some atypical antipsychotics can reduce the seizure threshold, and the study found that some atypical antipsychotics can inhibit the concentration-dependent chloride current caused by gamma-aminobutyric acid (GABA) in rat dorsal root ganglion neurons in vitro. At therapeutic concentrations, the inhibitory effect of buanserin on GABA was associated with clinical seizures (correlation coefficient of 0.82); In contrast, buanserin activates GABA to produce chloride currents at concentrations greater than 1 μmol/L-1. |
| pharmacokinetics | 1. Absorption and distribution oral administration of bunasserin in healthy volunteers (including single dose of bunasserin 4-12mg and 2mg? Times -1,bid * 10d), rapid absorption, cmax median time is less than or equal to 2H. Ten healthy volunteers taking 4mg/d-1 of bonanserin achieved steady-state plasma concentrations within 5 days. In the 8wk experiment (n = 19), the daily dose of bunanserin was 4~24mg, and the plasma concentration of schizophrenia patients was gradually increased after 1~2H, and related to drug dose. Overall analysis of 2 long-term trials (n = 135) showed that AUC0 ~ 24H was proportional to the daily dose (4~32mg); the study also found that the cmax and AUC of healthy volunteers increased with the increase of dose after a single dose of 4~12mg, but it was not proportional to the dose. 10 healthy volunteers repeatedly took 2mg of bonanserin? Cycle -1, bid, there was no significant aggregation of the prototype drug and no significant aggregation of drug metabolites compared to a single dose of 2mg. 2. Metabolism and excretion in vitro study data show that the metabolic pathway of bunanserin is very wide, mainly through CYP3A4 metabolism. The drug is metabolized by N-deethylation and N-oxidation of the piperazine ring and hydroxylation and oxidation of the cyclooctane ring, followed by binding to glucuronide to form hydroxylated metabolites. Among the major metabolites produced (N-deethylated, 7-hydroxylated, 8-hydroxylated bunanserin), N-desethylated bunanserin has the strongest neurotransmitter affinity in vitro, but the pharmacological activity of N-desethylated bunanserin is many times lower than that of the prodrug in animal models. The study found that 6 healthy Caucasian volunteers received 4mg of radiolabeled bunanserin, which was excreted mainly as metabolites in the urine (59%) and in the stool (30%), there are less than 5% of the drug to the prototype from the stool, urine did not detect the prototype drug. Table 1 shows the main pharmacokinetic parameters of bunanserin |
| drug interaction | since bonanserin is mainly metabolized by CYP3A4, drugs that inhibit CYP3A4, such as ketoconazole when taking it at the same time, it can increase the blood concentration of bunanserin, so it is necessary to pay attention to the combination of the two. For example, in a study of 12 healthy Caucasian volunteers, the peak mean plasma concentrations (cmax) in bunanserin were 2.5mg concomitantly with ketoconazole 400mg/d-1. There was a 13-fold increase and a 16-fold increase in the time required for the area under the drug plasma concentration-time curve (AUC) from 0 to the final equilibrium concentration. Other CYP3A4 inhibitors, such as erythromycin, clarithromycin, ciclosporin, and diltiazem, can also increase the effects of bunanserin and grapefruit juice. In the above study, when the bunanserin 2mg? d-1 and erythromycin 1200mg? d-1, Its cmax increased 2.4-fold and AUClast increased 2.5-fold; Both cmax and AUClast increased 1.8-fold when combined with grapefruit juice. It is also necessary to be careful to combine with the inducers of the benanserin and CYP3A4 enzyme, such as phenytoin, carbamazepine and rifampicin. In addition, bunanserin is not allowed to be used with epinephrine because it can cause severe hypotension; Nor should it be used with central nervous system sedatives such as barbiturates. |
| Application | is mainly used for the treatment of atypical psychosis |
| adverse reactions | 1. Malignant Syndrome serious side effects of antipsychotic drugs, especially in some high-potency low-dose antipsychotic drugs, among which haloperidol is the most reported. The main symptoms are: high fever, muscle rigidity, creatine phosphate kinase (CPK) increased. At the onset of this disease, the increase of white blood cells and the increase of creatine phosphate kinase (CPK) are common. The clinical causes of death are persistent fever, disturbance of consciousness, Dyspnea, circulatory collapse, dehydration symptoms, acute renal insufficiency and so on. Statistics show that during the course of administration of bunanserin there are fewer cases of malignant syndrome, the rate is much less than 5%. 2. Impact on the nervous system In the long-term treatment of patients with schizophrenia using bunanserin, tardive dyskinesia is less common. This symptom occurs on dose reduction as well as on or off administration, but the rate of onset of this symptom is less than 5%. In one study, bunanserin was found to cause significantly less tardive dyskinesia and dizziness than haloperidol; However, it was 1.6 times more likely to cause tardive dyskinesia than risperidone. 3. Effect on endocrine The effect of nanserin on prolactin was related to the course of treatment. In one study, the incidence of hyperprolactinemia was higher in patients studied on long-term use (20.9% to 34.4%), which was not significantly different from haloperidol. However, studies in patients with short-term use showed a significant reduction in the incidence of hyperprolactinemia in the bunanserin group compared to the risperidone group. On the body of alanine aminotransferase and aspartate aminotransferase, Bunanserin treatment group was significantly lower than risperidone group. 4. Other adverse reactions patients with schizophrenia were well tolerated in long-term use of bunanserin. In patients with long-term treatment, the incidence of adverse events was less (27.9% ~ 31.5%), and the incidence of serious adverse reactions was about 5.9% ~ 9.8%. Long-term treatment of the more common adverse reactions are affect urination (34.4%), dry mouth (14.8%), constipation (12.8), dizziness (11.5%) and so on. |
| atypical anti-schizophrenia drugs | schizophrenia is a common psychiatric disease, since the early 50's discovered the antipsychotic effect of chlorprozil. Schizophrenia has been dominated by drug therapy. At present, the commonly used antipsychotic drugs are divided into typical and atypical two categories according to the receptor blocking effect: typical antipsychotic drugs are represented by chlorpromazine and haloperidol. The main mechanism of action is to block dopamine receptors. They have a good effect on the positive symptoms of schizophrenia (hallucinations, delusions, excitement, agitation, Impulse behavior, etc.). At the same time, the extrapyramidal reaction (EPS) is common, and the negative symptoms (apathy, poor thinking, will, etc.), the effect on negative symptoms is obviously better than that of traditional drugs, with high safety, mild side effects, smaller dosage, and many more advanced dosage forms, which greatly improves the compliance of patients, representative drugs are clozapine, risperidone, olanzapine and so on. An 8-week, double-blind, clinical comparative trial of bunanserin and haloperidol in 263 patients with schizophrenia. At least as effective as 4-12mg/day haloperidol, both at 8-24mg/day of bunanserin and increasing the final overall improvement series (FGIR) scores (61.2% and 51.3% for at least moderate improvement, respectively), and fewer extrapyramidal adverse reactions (52.7% and 75.4%, respectively). |
| Domestic patent information | in January, 2008, bunanserin was developed and listed by sumitfinal Pharmaceuticals Corporation, Japan. This product is for 1989 of the compound patent. The patent has expired. At present, this product is not imported in China. According to the Patent Law and the regulation on administrative protection of pharmaceuticals, this drug does not have patent risk in China and does not have the conditions for applying for administrative protection in China. |
Last Update：2024-04-09 21:54:55
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Product Name: Blonanserin CRS Visit Supplier Webpage Request for quotationCAS: 132810-10-7
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Spot supply
Product Name: Blonanserin Visit Supplier Webpage Request for quotationCAS: 132810-10-7
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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